Bloodstream infections affect a huge patient population in the United States, with more than 250,000 cases reported each year. Patients with indwelling medical devices, such as central venous catheters (CVCs), are most at risk for these infections. Frequently, various microorganisms from the skin of the patient, or respective healthcare professional, can gain access through the catheter wound as a result of non-sterile conditions. Of these resulting bloodstream infections, Candida species account for 9% of all bloodstream infections and are associated with ˜40% mortality rate. The most commonly isolated fungal pathogen from bloodstream infections is Candida albicans, but the prevalence of other species, such as C. parapsdosis, C. glabrata, and C. tropicalis, is increasing.
Candida spp. pathogens possess an outer cell wall that is an important determinant of pathogenicity. The cell wall is primarily composed of carbohydrates and structurally is separated into two layers. The outer layer is composed mostly of N-linked glycans and mannoproteins and the inner layer is composed of, β-glucan and chitin. The complexity of the cell wall contributes to various pathogenic factors including adherence of the fungus and establishment of cross-talk with the host known as “glycan code.” Cell wall components are also found in the extracellular matrix secreted by Candida spp. biofilms, which can contaminate the synthetic material surfaces of indwelling medical devices. Candida spp. biofilm production of polysaccharides, such as β-glucan, contributes to the decreased susceptibility of biofilms to antifungal drugs by sequestering antifungal drugs.
Various antimicrobial impregnation approaches have been devised to prevent catheter infections. Catheter materials coated with chlorhexidine-silver sulfadiazine and minocycline/rifampin have shown trends in reduced infection rates, but their clinical effectiveness remains questionable. Other treatments, including the use of silver-impregnated subcutaneous collagen cuffs, have also failed to be effective in recent trials. CVC contamination generally requires removal and replacement of the device in addition to a prolonged course of antifungal drug therapy, which raises concerns regarding drug toxicity and development of antifungal resistance. Antifungal chemotherapy is also problematic, with increasing prevalence of resistance to azole and echinocandin drugs as well as well-known nephrotoxicity of amphotericin B. Due to the high morbidity and mortality rate of catheter-related Candida spp. bloodstream infections, strategies for preventing medical device contamination by fungal pathogens remains a top priority for infection control.